The role of Nrf2 in acute and chronic muscle injury

Abstract The nuclear factor erythroid 2-related factor (Nrf2) is considered as a master cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory, and detoxifying proteins. The role of Nrf2 in the pathophysiology of skeletal muscles has been evaluated in different experimental models, however, due to inconsistent data, we aimed to investigate how Nrf2 transcriptional deficiency (Nrf2 tKO ) affects muscle functions both in acute and chronic injury. The acute muscle damage was induced in mice of two genotypes – WT and Nrf2 tKO mice by cardiotoxin (CTX) injection. To investigate the role of Nrf2 in chronic muscle pathology, mdx mice that share genetic, biochemical, and histopathological features with Duchenne muscular dystrophy (DMD) were crossed with mice lacking transcriptionally active Nrf2 and double knockouts ( mdx /Nrf2 tKO ) were generated. We have observed slightly increased muscle degeneration and delayed regeneration in Nrf2 tKO mice after CTX treatment. Nevertheless, transcriptional ablation of Nrf2 in mdx mice did not significantly aggravate the most deleterious pathological hallmarks of DMD such as degeneration, inflammation, fibrotic scar formation, and decreased angiogenesis, as well as the number and proliferation of satellite cells. In conclusion, our analyses in both acute and chronic injury mouse models have revealed no significant influence of Nrf2 transcriptional deficiency on skeletal muscle regeneration and function.